A Single Neanderthal Gene Differentiates African from European Immune Systems

You would think that since we are actually all one race, the human race, we would have the same susceptibility to diseases. But in fact, there is tremendous variance among the immune systems of different peoples living in varying parts of the world. The likelihood of developing certain infections, autoimmune diseases, or inflammatory conditions varies greatly, depending on where in the world your ancestors hailed. The immune systems of those of African and European descent diverge for instance, due to the different health challenges each population faced, historically.

Now, two new studies published in the journal Cell, help us to understand more about these differences. African immune systems are by and large stronger than their European counterparts, researchers found. Some of these variations can be traced back on the genetic level to proto-Europeans interbreeding with Neanderthals, which weakened their immune systems, over Africans who did not.

Homo sapiens left Africa somewhere between 100,000 and 60,000 years ago, and encountered a Europe already colonized by Neanderthals. Eventually, the two interbred, and the immune responses of Neanderthals helped homo sapiens adapt to their new environment and the pathogens there. Sometime after, around 40,000 years ago, Neanderthals vanished from the Earth. Today 20% of the world population carries Neanderthal genes within them.

Since Europe had a colder climate, a subtler inflammatory response was sufficient, researchers believe. However, in Africa, pathogens are more robust and so a faster immune response was required to ensure survival. Though they may respond better to pathogens, having an African immune system does have a downside, a higher risk of an autoimmune disorders.

Lluis Quintana-Murci of Institut Pasteur and CNRS in Paris, led one study. He said their findings show that such differences are responses that have been transcribed into DNA. Since the single gene they discovered was passed on by Neanderthals already living in Europe, it is considered something that conveyed an evolutionary advantage.

The earliest homo sapiens to settle Europe interbred with Neanderthals and benefited from their immune systems.

RNA sequencing was used by Quintana-Murci and his team, to categorize immune cells called primary monocytes, taken from 200 participants, half of European and the other African ancestry. Researchers looked at how the cells would respond when encountering a certain bacteria or virus. Differences in gene activity within immune cells varied widely between populations. What differentiated these two studies from others is not only studying immune response but the gene expression behind them.

Quintana-Murci and colleagues found that changes in a single gene, adopted from Neanderthals, became integral in the modern day European immune system and how it responds to pathogens. This discovery offers substantial evidence pertaining to gene selection and immune response. Certain regulatory variants too came from Neanderthals, which Europeans “borrowed” when the two interbred. This all plays out in how a Caucasian immune system responds to viral infections.

Luis Barreiro was the senior author of the other study. Barreiro hails from University of Montreal and the CHU Sainte-Justine, also in Canada. He and his team tested how African and European immune systems, particularly cells known as primary macrophages, responded to live, pathogenic bacteria. The macrophages of 175 Americans, 80 African Americans and 95 Caucasians, were used. These cells were grown in dishes and then infected with either listeria or salmonella bacteria.

After infecting them, Barreiro and colleagues returned 24 hours later to see how each cell responded. Those of an African descent showed an inflammatory response three times faster than that of European Americans. But this also had a disadvantage. A more active immune system comes with a higher risk of autoimmune disorders, such as Crohn’s disease. This is why African American women are three times more likely to develop Lupus than white ones, for example. After that, researchers examined the genes behind these responses and found that 12,000 of them, approximately 30% of the total, were expressed differently between these two races.

More research will need to be conducted to see how immune systems of different races and ethnicities act in different ways. This research may someday lead to more personalized treatment options, properly tailored to the patient’s biology. Previously, the molecular and genetic basis for immune system differences has been a mystery, Bareiro said. This research illustrates how the history of natural selection continues to influence us to this day.

Everything about disease resistance does not reside with the genes, however. According to Barreiro, "Genetics explains only about 30% of the observed differences in immune responses.” Diet, exercise, environmental influences, smoking, and other factors, tell a lot more of the story. Barreiro added that future studies should quantify what exact influence genetics have, and to what extent lifestyle choices and other factors contribute to overall health. Another issue is the lack of diversity in genomic-wide studies. 80% of genetic and biological samples have come from Caucasians, a recent comment in the journal Nature pointed out. This study illustrates just how critical knowing such differences is.

To learn more about the exploits of our ancient ancestors and how it affects us today, click here:

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